Stereodivergent Synthesis of 3-Hydroxyprolines and 3-Hydroxypipecolic Acids via Ketoreductase-Catalyzed Dynamic Kinetic Reduction

We report a practical enzymatic approach for the stereoselective synthesis of hydroxylated cyclic amino acids. Using ketoreductases, cyclic ketoesters are converted with high diastereo- and enantioselectivity to all isomers of 3-hydroxyproline and 3-hydroxypipecolic acid via a dynamic kinetic reduction reaction. This work highlights the ability of enzymes to provide solutions to challenges in stereoselective synthesis.